Byrne M M, Gliem K, Wank U, Arnold R, Katschinski M, Polonsky K S, Göke B
Department of Internal Medicine, Philipps University, Marburg, Germany.
Diabetes. 1998 Aug;47(8):1259-65. doi: 10.2337/diab.47.8.1259.
Impaired glucose tolerance (IGT) and NIDDM are both associated with an impaired ability of the beta-cell to sense and respond to small changes in plasma glucose concentrations. The aim of this study was to establish if glucagon-like peptide 1 (GLP-1), a natural enteric peptide and potent insulin secretagogue, improves this defect. Two weight-matched groups, one with eight subjects having IGT (2-h glucose, 10.1 +/- 0.3 mmol/l) and another with seven subjects with diet-treated NIDDM (2-h glucose, 14.5 +/- 0.9 mmol/l), were studied on two occasions during a 12-h oscillatory glucose infusion, a sensitive test of the ability of the beta-cell to sense and respond to glucose. Glucose was infused with a mean rate of 4 mg x kg(-1) x min(-1), amplitude 33% above and below the mean rate, and periodicity of 144 min, with infusion of saline or GLP-1 at 0.4 pmol x kg(-1) x min(-1) for 12 h. Mean glucose levels were significantly lower in both groups during the GLP-1 infusion compared with during saline infusion: 9.2 +/- 0.4 vs. 6.4 +/- 0.1 mmol/l in the IGT subjects (P < 0.0004) and 14.6 +/- 1.0 vs. 9.3 +/- 0.7 mmol/l in NIDDM subjects (P < 0.0002). Despite this significant reduction in plasma glucose concentration, insulin secretion rates (ISRs) increased significantly in IGT subjects (513.3 +/- 77.6 vs. 583.1 +/- 100.7 pmol/min; P < 0.03), with a trend toward increasing in NIDDM subjects (561.7 +/- 122.16 vs. 642.8 +/- 128 pmol/min; P = 0.1). These results were compatible with enhanced insulin secretion in the presence of GLP-1. Spectral power was used as a measure of the ability of the beta-cell to secrete insulin in response to small changes in the plasma glucose concentration during the oscillatory infusion. Spectral power for ISR increased from 2.1 +/- 0.9 during saline infusion to 7.4 +/- 1.3 during GLP-1 infusion in IGT subjects (P < 0.004), but was unchanged in NIDDM subjects (1.0 +/- 0.4 to 1.5 +/- 0.6; P = 0.3). We concluded that low dosage GLP-1 improves the ability of the beta-cell to secrete insulin in both IGT and NIDDM subjects, but that the ability to sense and respond to subtle changes in plasma glucose is improved in IGT subjects, with only a variable response in NIDDM subjects. Beta-cell dysfunction was improved by GLP-1 infusion, suggesting that early GLP-1 therapy may preserve beta-cell function in subjects with IGT or mild NIDDM.
糖耐量受损（IGT）和非胰岛素依赖型糖尿病（NIDDM）均与β细胞感知和响应血浆葡萄糖浓度微小变化的能力受损有关。本研究的目的是确定胰高血糖素样肽1（GLP - 1），一种天然的肠肽和强效胰岛素促分泌剂，是否能改善这一缺陷。将体重匹配的两组受试者进行研究，一组8名患有IGT的受试者（2小时血糖，10.1±0.3 mmol/L），另一组7名接受饮食治疗的NIDDM受试者（2小时血糖，14.5±0.9 mmol/L），在12小时的振荡葡萄糖输注期间进行两次测试，这是一种对β细胞感知和响应葡萄糖能力的敏感测试。葡萄糖以平均速率4 mg·kg⁻¹·min⁻¹输注，幅度在平均速率上下33%，周期为144分钟，在0.4 pmol·kg⁻¹·min⁻¹的剂量下输注生理盐水或GLP - 1 12小时。与输注生理盐水期间相比，两组在输注GLP - 1期间的平均血糖水平均显著降低：IGT受试者中为9.2±0.4 vs. 6.4±0.1 mmol/L（P < 0.0004），NIDDM受试者中为14.6±1.0 vs. 9.3±0.7 mmol/L（P < 0.0002）。尽管血浆葡萄糖浓度有显著降低，但IGT受试者的胰岛素分泌率（ISR）显著增加（513.3±77.6 vs. 583.1±100.7 pmol/min；P < 0.03），NIDDM受试者有增加趋势（561.7±122.16 vs. 642.8±128 pmol/min；P = 0.1）。这些结果与GLP - 1存在时胰岛素分泌增强一致。频谱功率被用作衡量β细胞在振荡输注期间响应血浆葡萄糖浓度微小变化而分泌胰岛素能力的指标。IGT受试者中，ISR的频谱功率从输注生理盐水期间的2.1±0.9增加到输注GLP - 1期间的7.4±1.3（P < 0.004），但NIDDM受试者中未改变（1.0±0.4至1.5±0.6；P = 0.3）。我们得出结论，低剂量GLP - 1可改善IGT和NIDDM受试者中β细胞分泌胰岛素的能力，但IGT受试者感知和响应血浆葡萄糖细微变化的能力得到改善，而NIDDM受试者只有可变反应。输注GLP - 1可改善β细胞功能障碍，表明早期GLP - 1治疗可能在IGT或轻度NIDDM受试者中保留β细胞功能。
